Pharmaceutical composition for preventing or treating cancer comprising ksp inhibitor and mitosis inhibitor

a technology of mitosis inhibitor and pharmaceutical composition, which is applied in the direction of drug compositions, genetic material ingredients, biochemistry apparatus and processes, etc., can solve the problems of unreported research, the anti-cancer drugs inhibiting ksp cannot obtain significant clinical trials results, and the apoptosis of cancer cells, so as to achieve synergistic effects on anti-cancer activity, inhibit the expression of ksp, and facilitate the effect of anti-cancer activity

Pending Publication Date: 2021-08-26
KOREA INST OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0052]The pharmaceutical composition for preventing or treating a cancer including an agent, which is capable of inhibiting expression of KSP, and a mitosis inhibitor according to the present invention may simultaneously inhibit the expression of KSP and a substitution effect of Kif15 for KSP; may induce synergistic effects on an anti-cancer activity when compared to treatment with the agent capable of inhibiting expression of KSP or the mitosis inhibitor alone; and may also have a therapeutic effect on a cancer resistant to a cancer therapeutic agent having a mitosis inhibiting activity. Accordingly, the pharmaceutical composition of the present invention can be widely used for anti-cancer therapy more efficiently.

Problems solved by technology

Paclitaxel is known to inhibit division of cancer cells by suppressing a mitotic spindle assembly (MSA), resulting in apoptosis of cancer cells.
However, such anti-cancer drugs inhibiting KSP could not obtain significant results in clinical trials (Chandrasekaran G, et al., Br J Cancer 2015, 113, 693-8; Myers S M, Collins I, Future Med Chem 2016, 8, 463-89).
However, research therefor has not been reported yet.

Method used

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  • Pharmaceutical composition for preventing or treating cancer comprising ksp inhibitor and mitosis inhibitor
  • Pharmaceutical composition for preventing or treating cancer comprising ksp inhibitor and mitosis inhibitor
  • Pharmaceutical composition for preventing or treating cancer comprising ksp inhibitor and mitosis inhibitor

Examples

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Effect test

example 1

Manufacture of Anti-Cancer Preparation Containing KSP siRNA and Paclitaxel

example 1-1

Manufacture of KSP siRNA-Containing Preparation

[0093]First, a PEGylated DC-Chol / DOPE cationic liposome was prepared using a known thin-film hydration method (Lee J, et al., Theragnosis 2016, 6, 192-203). DC-Chol, DOPE, and mPEG2000-DSPE were mixed in a ratio of 48.75:48.75:2.5 (molar ratio) such that a total weight of the mixture was approximately 300 μg, and chloroform was removed therefrom by lyophilization for 12 hours, thereby preparing a PEGylated liposome in the form of dry lipid film.

[0094]Subsequently, a PEGylated liposome into which KSP siRNA is introduced was prepared. Approximately, KSP siRNA consisting of nucleotides of SEQ ID NOS: 1 and 2 and a PBS buffer (containing 5% glucose, 10 mM, pH 7.4) were added to the PEGylated liposome in the dry lipid film form, followed by sonication for 30 seconds and stirring at room temperature for 4 hours to obtain a mixture. Herein, a mixing ratio of the PEGylated liposome and KSP siRNA was set in various ranges (20:1, 40:1, 60:1, 80:1...

example 1-2

Manufacture of Paclitaxel-Containing Preparation

[0100]A PEGylated liposome was prepared using the known thin-film hydration method (Lee J, et al., Theragnosis 2016, 6, 192-203). DC-Chol, DOPE, and mPEG2000-DSPE were mixed in a ratio of 48.75:48.75:2.5 (molar ratio) such that a total weight of the mixture was approximately 300 μg to obtain a lipid mixture, and paclitaxel was added to the obtained lipid mixture, thereby obtaining a final mixture. Chloroform was removed from the obtained final mixture by lyophilization for 12 hours to prepare a paclitaxel-containing PEGylated liposome.

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Abstract

The present invention relates to a method of treating a cancer including administering a pharmaceutical composition to an individual suspected to have the cancer excluding humans in a pharmaceutically effective amount, where the pharmaceutical composition comprises an agent capable of inhibiting expression of kinesin spindle protein (KSP) and a mitosis inhibitor.

Description

TECHNICAL FIELD[0001]The present invention relates to a pharmaceutical composition for preventing or treating a cancer, which includes a kinesin spindle protein (KSP) inhibitor and a mitosis inhibitor, and more particularly, to a pharmaceutical composition for preventing or treating a cancer, which includes an agent capable of inhibiting expression of KSP and a mitosis inhibitor such that a substitution effect for KSP occurring when KSP is inhibited is also inhibited; a method of treating a cancer using the pharmaceutical composition; a pharmaceutical composition for preventing or treating a cancer resistant to a cancer therapeutic agent; and a method of treating a cancer resistant to a cancer therapeutic agent using the pharmaceutical composition.BACKGROUND ART[0002]A cancer (malignant tumor) is a major disease showing the highest mortality rate in modern society and no breakthrough treatment therefor has been developed yet despite extensive research to date. Although treatment usi...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/517A61K31/337A61K31/404C12N15/113
CPCA61K31/517A61K31/337A61K45/06C12N15/113A61K31/404C12N2310/14C12N2320/31A61K48/00A61K31/713A61P35/00A61K2300/00
Inventor AHN, HYUNG JUN
Owner KOREA INST OF SCI & TECH
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